Sequencing Therapy in Metastatic BRAF+ Melanoma

Source: OncLive,October 2019

Hussein A. Tawbi, MD, PhD: In metastatic melanoma, testing for the BRAF mutation is very important up front, so we know if our patients have the option of being treated with targeted therapy. All the currently approved therapies in the metastatic setting have actually been approved in the first-line setting. BRAF/MEK inhibition was dabrafenib-trametinib, vemurafenib-cobimetinib, and now encorafenib-binimetinib. All 3 combinations have been tested in the first-line setting.

Nivolumab—single-agent. Ipilimumab—single-agent. Pembrolizumab—single-agent. These are all approved in the first-line setting. And then we have data on nivolumab in combination with ipilimumab, where we have some improvement in PFS [progression-free survival] and a modest improvement in OS [overall survival]. Again, the combination is approved in the first-line setting. Technically, all the data we have at our disposal is really for: What do you start your patients with? What happens to your patient if you start with a certain therapy first? We don’t have great data to guide us on what to do in the second-line setting. I think that is actually where a lot of the confusion and a lot of the debate on what you should start with comes from.

What we do know is targeted therapy is highly effective and it works very quickly but also has a limited duration of response. What we know from immunotherapy is that you have potentially lower response rates if you start with a single-agent option. However, almost every response that you get with immunotherapy tends to be more durable if not very durable. If you can achieve a complete response, for instance, with immunotherapy, those responses look as if they’re durable for many years. Partial responses seem to be durable, but some of those patients can still progress.